Adherence and persistence in allergen immunotherapy (APAIT): A reporting checklist for retrospective studies.

BACKGROUND: Adherence is essential for the long-term efficacy of allergen immunotherapy (AIT) and has been evaluated in numerous retrospective studies. However, there are no published guidelines for best practice in measuring and reporting adherence or persistence to AIT, which has resulted in substantial heterogeneity among existing studies. The 'adherence and persistence in AIT (APAIT)' checklist has been developed to guide the reporting, design and interpretation of retrospective studies that evaluate adherence or persistence to AIT in clinical practice. METHODS: Five existing checklists, focussing on study protocol design, the use of retrospective databases/patient registries, and the appraisal and reporting of observational studies, were identified and merged. Relevant items were selected and tailored to be specific to AIT. The content of the checklist was discussed by 11 experts from Europe, the United States and Canada, representing allergy, healthcare and life sciences, and health technology appraisal. RESULTS: The APAIT checklist presents a set of items that should either be included or at least considered, when reporting retrospective studies that assess adherence or persistence to AIT. Items are organized into four categories comprising study objective, design and methods, data analysis, and results and discussion. The checklist highlights the need for clarity and transparency in reporting and emphasizes the importance of considering potential sources of bias in retrospective studies evaluating adherence or persistence to AIT. CONCLUSIONS: The APAIT checklist provides a pragmatic guide for reporting retrospective adherence and persistence studies in AIT. Importantly, it identifies potential sources of bias and discusses how these influence outcomes.

Oral immunotherapy as a curative treatment for food-allergic preschool children: Current evidence and potential underlying mechanisms.

The worldwide rising prevalence of food allergy is a major public health concern. Standard care consists of allergen avoidance and rescue medication upon accidental exposure. Oral immunotherapy (OIT) is increasingly being studied as a treatment option. Although desensitization (an increased reaction threshold) is often achieved during OIT, sustained unresponsiveness (SU; clinical nonreactivity after finishing OIT) is not achieved in most patients. A few studies have investigated the effectiveness of OIT in children younger than 4 years of age (early = e-OIT) and have shown a much more favorable outcome in terms of SU development. Together with food allergy prevention studies, which have demonstrated high efficacy of early oral allergen exposure, the outcomes of e-OIT studies indicate an early-life window of opportunity to achieve SU, allowing unrestricted dietary intake. However, the underlying mechanism of the high effectiveness of e-OIT is not understood yet. Both cohort and OIT studies indicate early-life immune plasticity. An immature food-allergic response in the first years of life seems to be a major driver of this immune plasticity, along with a higher tolerogenic immunological state. Allergy maturation can likely be disrupted effectively by early intervention, preventing the development of persistent food allergy. Upcoming studies will provide important additional data on the safety, feasibility, and effectiveness of e-OIT. Combined with immune mechanistic studies, this should inform the implementation of e-OIT.

Reactions to peanut at first introduction in infancy are associated with age ≥8 months and severity of eczema.

BACKGROUND: Previous studies have shown the efficacy of the early introduction of peanut to prevent peanut allergy. Due to the exclusion of infants with sensitization to peanut, it remains unclear what the optimal timing of introduction is. METHODS: The PeanutNL study was performed in 6 pediatric allergology centers in the Netherlands. Infants referred for the clinical early introduction of peanut to prevent peanut allergy underwent skin prick tests for peanut and an oral peanut challenge at a median age of 6 months. RESULTS: One hundred sixty two of 707 infants (23%) who had never eaten peanut before were sensitized to peanut, of which 80 (49%) had wheals of >4 mm. Sixty seven of 707 infants (9.5%) had a positive oral challenge to peanut at first introduction. Multivariate analysis revealed that age (p < .001) and SCORAD eczema severity scores (p = .001) were significant risk factors. Introduction of peanut at ≥8 months in infants with moderate and severe eczema resulted in an increased risk (odds ratio 5.24 (p = .013) and 3.61 (p = .019), respectively) of having reactions to peanut as compared to introduction before 8 months. A family history of peanut allergy and previous reactions to egg were not identified as independent risk factors. CONCLUSION: These results suggest that peanut should be introduced before the age of 8 months to reduce the risk of reactions at first exposure in infants with moderate and severe eczema. Furthermore, since children with severe eczema have the highest risk of reactions, the clinical introduction of peanut should be considered, at the latest at the age of 7 months.

Question 6: What is the use of allergy testing in children with asthma?

Disagreement exists between asthma guidelines on the routine use of allergy testing in the diagnostic work-up of a child with persistent asthma, although the important role of inhalant allergy in the pathophysiology of asthma and allergic rhinitis is undisputed. The usefulness of screening for inhalant allergies in asthma is connected to the efficacy of allergen reduction measures and specific immunotherapy, both of which appear to be more effective in children than in adults. Allergen-specific exposure reduction recommendations are therefore an essential part of childhood asthma management. Such recommendations should be guided by appropriate diagnosis of inhalant allergy, based on a structured allergy history and results of sensitization tests. Specific IgE testing and skin prick testing show comparable results in identifying clinically important sensitizations. Although a therapeutic medication trial can be started pragmatically in children with asthma without diagnosing their inhalant allergy, we recommend making or excluding an accurate diagnosis of inhalant allergy.

Is the MARS questionnaire a reliable measure of medication adherence in childhood asthma?

OBJECTIVE: To assess the reliability of the Medication Adherence Report Scale (MARS-5) for assessing adherence in clinical practice and research. METHODS: Prospective cohort study following electronically measured inhaled corticosteroids (ICS) adherence for 1 year in 2-13-year-old children with persistent asthma. The relationship between electronically measured adherence and MARS-5 scores (ranging from 5 to 25) was assessed by Spearman's rank correlation coefficient. A ROC (receiver operating characteristic) curve was performed testing MARS-5 against electronically measured adherence. Sensitivity, specificity, positive and negative likelihood ratios of the closest MARS-5 cut-off values to the top left-hand corner of the ROC curve were calculated. RESULTS: High MARS scores were obtained (median 24, interquartile range 22-24). Despite a statistically significant correlation between MARS-5 and electronically assessed adherence (Spearman's rho = 0.47; p < 0.0001), there was considerable variation of adherence rates at every MARS-5 score. The area under the ROC curve was 0.7188. A MARS-5 score ≥23 had the best predictive ability for electronically assessed adherence, but positive and negative likelihood ratios were too small to be useful (1.65 and 0.27, respectively). CONCLUSIONS: Self-report using MARS-5 is too inaccurate to be a useful measure of adherence in children with asthma, both in clinical practice and in research.

Non-adherence in children with asthma reviewed: The need for improvement of asthma care and medical education.

Adherence to daily inhaled corticosteroid therapy is a key determinant of asthma control. Therefore, improving adherence to inhaled corticosteroids is the most effective method through which healthcare providers can help children with uncontrolled asthma. However, identifying non-adherent patients is difficult, and electronic monitoring is the only reliable method to assess adherence. (Non-)adherence is a complex behavioural process influenced by many interacting factors. Intentional barriers to adherence are common; driven by illness perceptions and medication beliefs, patients and parents deliberately choose not to follow the doctor's recommendations. Common non-intentional barriers are related to family routines, child-raising issues, and to social issues such as poverty. Effective interventions improving adherence are complex, because they take intentional and non-intentional barriers to adherence into account. There is evidence that comprehensive, guideline-based asthma self-management programmes can be successful, with excellent adherence and good asthma control. Patient-centred care focused on healthcare provider-patient/parent collaboration is the key factor determining the success of guided self-management programmes. Such care should focus on shared decision-making as this has been shown to improve adherence and healthcare outcomes. Current asthma care falls short because many physicians fail to adhere to asthma guidelines in their diagnostic approach and therapeutic prescriptions, and because of the lack of application of patient-centred health care. Increased awareness of the importance of patient-centred communication and increased training in patient-centred communication skills of undergraduates and experienced attending physicians are needed to improve adherence to daily controller therapy and asthma control in children with asthma.

It's the adherence, stupid (that determines asthma control in preschool children)!

Although guideline-based asthma care and adherence to inhaled corticosteroids are predictors of asthma control, the role of adherence in maintaining long-term asthma control is largely unknown. This study was designed to explore the relationship between adherence to inhaled corticosteroids and long-term asthma control in young children with asthma. In this observational study, 81 2-6-year-old asthmatic children, using inhaled corticosteroids, closely followed-up in a programme with extensive self-management training, were enrolled. Adherence was measured daily for 12 months using Smartinhaler (Nexus6 Ltd, Auckland, New Zealand) devices. Long-term asthma control was assessed by parents and physicians and included clinical assessment, an asthma control questionnaire and lung function measurement. We examined the association of adherence to asthma control, adjusting for seasonal influences and clinical characteristics. Median (interquartile range) adherence was 87% (70-94%), and 64 (79%) children had well-controlled asthma throughout follow-up. Adherence >80% was associated with better asthma control, and we found no important confounders of this association. Children with persistent mild symptoms had lower adherence rates (p=0.028). Guideline-based asthma care was associated with good asthma control in most children. Adherence to inhaled corticosteroids was an independent strong predictor of long-term asthma control, with highest levels of asthma control found in children with adherence >80% of doses prescribed.

Every parent tells a story: why non-adherence may persist in children receiving guideline-based comprehensive asthma care.

OBJECTIVE: Effective self-management and adherence to inhaled corticosteroids are issues of particular interest in comprehensive asthma care. In spite of this care, however, a number of parents and children remain non-adherent. The reasons for this non-adherence have up till now been unknown, because previous adherence studies have based their findings either on populations with poor adherence or on unreliable self-reported adherence. This study was designed to explore factors that contribute to persistent non-adherence to inhaled corticosteroids in children ranging between 2 and 12 years of age receiving comprehensive asthma care, with adherence assessed objectively. METHODS: This qualitative study was based on in-depth interviews which took place in the homes of parents whose children had completed a one-year follow-up of electronically measured adherence to inhaled corticosteroids. Rich and comprehensive descriptions of parents' own accounts of self-management behavior were obtained using active listening techniques. Each interview was recorded and transcribed verbatim followed by data analysis using standard methodology for qualitative studies. RESULTS: Twenty children's parents (mean age 5.9 years) were interviewed. Distinctive patterns of modifiable barriers to adherence emerged, including a novel finding of parents misjudging their child's ability to manage the daily use of medication by him/herself. Persistent non-adherence appeared to be caused by a number of maintaining factors. Most noticeable factors were unawareness of non-adherence by both parents and health care providers, a lack of parental drive to achieve high adherence and ineffective parental problem-solving behaviour. CONCLUSIONS: This study has identified modifiable barriers to adherence in families participating in a comprehensive asthma care programme. Future studies are needed to verify our novel findings and to investigate whether interventions around these barriers are needed to increase the effectiveness of asthma care programs.

Using communication skills to improve adherence in children with chronic disease: the adherence equation.

Nonadherence to maintenance medication is common in paediatric chronic conditions. Despite the common belief that nonadherence is therapy-resistant, and the apparent lack of evidence for successful interventions to improve adherence, there is, in fact, a considerable body of evidence suggesting that adherence can be improved by applying specific communicative consultation skills. These can be summarized as the adherence equation: adherence=follow-up+dialogue+barriers and beliefs+empathy and education => concordance. Close follow-up of children with a chronic condition is needed to establish a therapeutic partnership with the family. Teaching self management skills is not a unidirectional process of providing information, but requires a constructive and collaborative dialogue between the medical team and the family. Identifying barriers to adherence can be achieved in a non-confrontational manner, by showing a genuine interest what the patient's views and preferences are. In particular, parental illness perceptions and medication beliefs should be identified, because they are strong drivers of nonadherence. Through empathic evidence-based education, such perceptions and beliefs can be modified. By applying these strategies, concordance between the child's family and the medical team can be achieved, resulting in optimal adherence to the jointly created treatment plan.

High inhaled corticosteroids adherence in childhood asthma: the role of medication beliefs.

Our aim was to study determinants of adherence in young asthmatic children over a 3-month period, including the role of parental illness and medication perceptions as determinants of adherence. Consecutive 2-6-yr-old children with asthma, using inhaled corticosteroids (ICS), followed-up at our paediatric asthma clinic (where patients are being extensively trained in self-management, and are followed-up closely) were enrolled. Adherence was measured electronically using a Smartinhaler® and calculated as a percentage of the prescribed dose. We examined the association of adherence to a range of putative determinants, including clinical characteristics and parental perceptions about illness and medication. Median (interquartile range) adherence, measured over 3 months in 93 children, was 92 (76-97)%, and most children had well controlled asthma. 94% of parents expressed the view that giving ICS to their child would protect him/her from becoming worse. Adherence was significantly associated with asthma control and with parental perceptions about medication. The high adherence rate observed in our study was associated with parental perceptions about ICS need. The high perceived need of ICS may probably be ascribed to the organisation of asthma care (with repeated tailored education and close follow-up).

Preschool children with high adherence to inhaled corticosteroids for asthma do not show behavioural problems.

AIM: To assess prevalence of behavioural problems in preschool children with asthma with electronically verified exposure to inhaled corticosteroids (ICS). METHODS: Cross-sectional study of 81 children 2-5 years of age using daily ICS for persistent asthma. During 3 months' follow-up, adherence to ICS treatment was recorded by an electronical logging device (Smartinhaler(®)). Parents completed the Child Behavior Checklist 1.5-5 years (CBCL 1.5-5) to assess behavioural problems; results were compared to a published reference group of healthy children. RESULTS: The median (interquartile range) adherence to ICS was 92 (78-97) %. There was no difference in total CBCL score between children with asthma on ICS (mean, [SD] 32.10 [1.99]) and the reference group (33.30 [1.87], 95% CI for difference -6.62 to 4.22). Children with asthma were more likely to have somatic complaints (95% CI for difference 0.64 to 1.96) and less likely to have anxious/depressive symptoms (95% CI for difference -1.57 to -0.25) than the reference group. CBCL scores were not significantly related to the electronically measured adherence rates. CONCLUSIONS: Maintenance treatment with ICS, taken daily as prescribed, is not associated with an increased risk of behavioural problems in preschool children.

[Nasal toilet in infants with rhinitis: nasal passage crucial, so treat with xylometazoline]. / Neustoilet bij zuigelingen met rinitis.

A good nasal passage is crucial for neonates and infants, as they rely on obligate nasal breathing. Feeding problems and dyspnoea are commonly seen in infants with nasal obstruction.In this article, we emphasize the importance of relieving nasal congestion caused by an infection. An effective therapy to reduce nasal obstruction, caused by mucus, is rinsing with saline. Xylometazoline can be added if the effect of saline is insufficient. However, guidelines are often cautious with prescribing nasal decongestants in infants. These recommendations are mainly based on case reports, and often concern overdoses or other medication than xylometazoline. The risk of severe side effects with xylometazoline in young children is low if the dosage is adequate.

Parental illness perceptions and medication perceptions in childhood asthma, a focus group study.

AIM: Asthma treatment according to guidelines fails frequently, through patients' nonadherence to doctors' advice. This study aimed to explore how differences in asthma care influence parents' perceptions to inhaled corticosteroids (ICS). METHODS: We conducted six semistructured focus groups, including 44 parents of asthmatic children (2-12 years of age, treated in primary or specialist care). Verbatim transcripts were analysed with standard qualitative research methods. RESULTS: Parents decided deliberately whether ongoing ICS use was useful for their child. This decision was based on their perceptions about illness and medication. In primary care, this issue was hardly ever discussed with the health care provider because regular scheduled follow-up was unusual. In specialist care, regular scheduled follow-up was usual, and parental perceptions about illness and medication were discussed and modified when needed. Parent-reported adherence was lower in primary care than in specialist care. CONCLUSION: This focus group study illustrates how strongly parental perceptions of illness and medication influence adherence to health care providers' advice and that such perceptions can be modified within a strong doctor-patient partnership, improving adherence.

Height growth in children with asthma treated with guideline-recommended dosages of fluticasone and electronically assessed adherence.

BACKGROUND AND AIMS: Inhaled corticosteroids (ICS) reduce growth during the first year of treatment, but this growth suppressing effect does not continue during further treatment. Decreasing adherence may play a role in explaining this. The aim of this study was to examine the relationship between cumulative real exposure (with objectively assessed adherence) to ICS and height growth in children with asthma. METHODS: We investigated 99 prepubertal children with asthma, 2-13 years of age, who had been using ICS in guideline-recommended dosages for ≥3 months, and continued to do so during 1-year follow-up. ICS adherence was assessed by electronic monitoring devices, allowing calculation of true cumulative exposure to ICS. We analysed the relationship between cumulative ICS dose and height growth velocity (assessed as change in height SD score) over 1 year. RESULTS: Median (IQR) adherence over 1 year was 84 (68-92) %. Mean cumulative fluticasone dose was 64.6 (SD, 27.8) mg, reflecting a daily dose of 167 (SD, 7) µg. The negative correlation between cumulative ICS dose and height growth velocity (r=-0.266; p=0.008) became non-significant after adjustment for age and sex in a multiple regression model (adjusted r=-0.188; p=0.066). CONCLUSIONS: One year of ICS treatment in guideline-recommended dosages with high adherence did not result in significant or relevant growth suppression. Unaffected growth can be maintained for at least 1 year in children with asthma during ICS treatment with high adherence.

Long-term adherence to daily controller medication in children with asthma: The role of outpatient clinic visits.

OBJECTIVE: To investigate changes in inhaled corticosteroids adherence, both before and after a scheduled follow-up visit, in young children in a comprehensive asthma management program. STUDY DESIGN: One-year prospective follow-up study in 104 asthmatic children (mean age 4.8 years). Adherence to inhaled corticosteroids was assessed using electronic (Smartinhaler®) devices. We assessed changes in adherence before and after clinic visits. A > 10% increase in adherence in the 3 days preceding a clinic visit was considered to reflect clinically relevant white coat adherence (WCA) if it exceeded background variation in adherence (median change >0, and increase larger than adherence changes after a clinic visit). RESULTS: Overall adherence was high (median 85%). A pre-visit increase in adherence of >10% was demonstrated in 17 patients (22%), but the median change in adherence around a clinic visit was 0. There were no significant differences in changes in adherence between the days before or after a visit (P > 0.2). The median coefficient of variation in adherence was 9%, and did not significantly differ between children with and without a pre-visit increase in adherence (P = 0.12). Twelve patients (15.4%) showed an increase of adherence in the month following a clinic visit; their overall mean (SE) adherence was slightly lower (73% (4.6%)) than those without such an increase (80% (2.2%), P = 0.054). CONCLUSIONS: There was no WCA in children with asthma enrolled in a comprehensive asthma management program with high overall adherence. This suggests that WCA in pediatric chronic conditions primarily occurs against the background of low overall adherence.

Long-term adherence to inhaled corticosteroids in children with asthma: Observational study.

INTRODUCTION: Non-adherence to daily controller medication in childhood asthma is strongly dependent on potentially modifiable factors such as parental illness perceptions and medication beliefs. The extent to which adherence in children can be improved by addressing modifiable determinants of non-adherence has not been studied to date, however. We assessed long-term adherence and its determinants in children with asthma enrolled in a comprehensive asthma care program employing shared decision making with parents. METHODS: Observational study in 135 children 2-12 years of age with asthma attending a hospital-based outpatient clinic. One-year adherence to inhaled corticosteroids was measured by electronic devices. Parental illness perceptions and medication beliefs, and asthma control were assessed by validated questionnaires. RESULTS: Median (interquartile range) adherence was 84% (70-92%). 55 children (41%) did not achieve the pre-defined level of good adherence (≥80%) and this was associated with poorer asthma control. Parental perceived medication necessity was high, with a median (interquartile range) BMQ necessity score of 17 (16-20). Parents' replies to the five key questions on the core issues of the program showed high concordance of their illness perceptions and medication beliefs with the medical model of asthma and its treatment. Differences in these perceptions between adherent and non-adherent families were small and non-significant. CONCLUSIONS: Poor adherence may persist in children despite a high level of concordance between medical team and parents on illness perceptions and medication beliefs, even in the absence of socio-economic barriers to good adherence. Achieving good adherence in all children is a complex task, requiring interventions not covered in current guidelines of managing asthma in children.

General practitioners' prescribing behaviour as a determinant of poor persistence with inhaled corticosteroids in children with respiratory symptoms: mixed methods study.

OBJECTIVES: To evaluate general practitioners' (GPs') prescribing behaviour as a determinant of persistence with and adherence to inhaled corticosteroids (ICS) in children. DESIGN: Prospective observational study of persistence with and adherence to ICS followed by a focus group study of the GPs prescribing this treatment. SETTING: 7 primary care practices in the area of Zwolle, the Netherlands. PARTICIPANTS: 134 children aged 2-12 years had been prescribed ICS in the year before the study started by their 19 GPs. MAIN OUTCOME MEASURES: Patterns and motives of GPs' prescribing behaviour and the relationship with persistence with and adherence to ICS. RESULTS: GPs' prescribing behaviour was characterised by prescribing short courses of ICS to children with various respiratory symptoms without follow-up for making a diagnosis of asthma. This was driven by the GPs' pragmatic approach to deal with the large number of children with respiratory symptoms, and by beliefs about ICS which differed from currently available evidence. This prescribing behaviour was the main reason why 68 (51%) children did not persist with the use of ICS. In children with persistent use of ICS and a GP's advice to use ICS on a daily basis, the median (IQR) adherence was 70% (41-84%), and was similar for patients with persistent asthma and children lacking a diagnosis or symptoms of asthma. CONCLUSIONS: Inappropriate prescription of ICS to children by GPs is common and drives the lack of persistence with ICS therapy in primary care. This finding should be taken into account when interpreting data from large prescription database studies. Improving primary healthcare providers' knowledge and competence in diagnosing and managing asthma in children is needed.

[A newborn with an abnormal position of the forearm]. / Een neonaat met een afwijkende stand van de onderarm.

A girl was born with a deformed position of the left forearm in pronation. On examination, supination was highly limited. Conventional radiography revealed a proximal radioulnar synostosis. The right forearm showed no abnormalities. Radioulnar synostosis is a pathological connection between the radius and the ulna, usually located in the proximal forearm. In 60% of the patients, this congenital lesion presents bilaterally.